Phase II study of tailored S-1 monotherapy with a 1-week interval after a 2-week dosing period in elderly patients with advanced non-small cell lung cancer

Background

S-1 is an oral fluoropyrimidine that is active in the treatment of non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and appropriate dose adjustments of S-1 in elderly patients have not yet been established.

Natural History and Predictors of Progression to Sjögren's Syndrome Among Participants of the Sjögren's International Collaborative Clinical Alliance Registry

Objective

To explore changes in the phenotypic features of Sjögren's syndrome (SS), and in SS status among participants in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry over a 2–3‐year interval.

Methods

All participants in the SICCA registry who were found to have any objective measures of salivary hypofunction, dry eye, focal lymphocytic sialadenitis in minor salivary gland biopsy, or anti‐SSA/SSB antibodies were recalled over a window of 2 to 3 years after their baseline examinations to repeat all clinical examinations and specimen collections to determine whether there was any change in phenotypic features and in SS status.

Results

As of September 15, 2013, a total of 3,514 participants had enrolled in SICCA, and among 3,310 eligible, 771 presented for a followup visit. Among participants found to have SS using the 2012 American College of Rheumatology (ACR) classification criteria, 93% again met the criteria after 2 to 3 years, and this proportion was 89% when using the 2016 ACR/European League Against Rheumatism (EULAR) criteria. Among those who did not meet ACR or ACR/EULAR criteria at baseline, 9% and 8%, respectively, had progressed and met them at followup. Those with hypergammaglobulinemia and hypocomplementemia at study entry were, respectively, 4 and 6 times more likely to progress to SS by ACR criteria than those without these characteristics (95% confidence interval 1.5–10.1 and 1.8–20.4, respectively).

Conclusion

While there was stability over a 2–3‐year period of both individual phenotypic features of SS and of SS status, hypergammaglobulinemia and hypocomplementemia at study entry were predictive of progression to SS.

     

Relationship of Plasma IL-6 to the Metabolic Measures associated with Insulin Resistance due to Adiposity

Objectives To elucidate the relationship of plasma interleukin-6 (IL-6) to the metabolic measures associated with insulin resistance (IR) due to adiposity. Methods For a cross-sectional study, eighty normotensive men with and without obe-sity were enrolled consecutively in our health examination center. Fasting blood glucose (FBG), fasting plasma immunoreactive insulin (FIRI), HOMA-R (Homeostasis Model Assessment Insulin Resistance Index), plasma lipids (cholesterol, triglyceride, highdensity lipoprotein cholesterol), cortisol, dehydroepiandrosterone-sulfate (DHEA-S), interleukin-6 and C-reactive protein(CRP) were measured. Results Plasma levels of FIRI, triglyceride fiG), DHEA-S, CRP and HOMA-R were significantly higher inobese group with BMI over 25 than non-obese group, whereas HDL-C was significantly lower in obese group. BMI was positively correlated with FIRI, TG, hsCRP and HOMA-R, whereas negatively with HDL-C. BMI was positively correlated with plasma DHEA-S levels but not with cortisol. Plasma levels of IL-6 were positively correlated with FIRI, TG, CRP and HOMA-R but in a multiple regression analysis with IL-6, only HOMA-R and TG remained explainable variables. Conclusions Each of commonly used mea-sures of inflammatory reaction, CRP and IL-6, showed a significantly positive correlation with either FIRI or HOMA-R, suggesting associations between subclinical inflammation and obesity as the risk of type 2 diabetes mellitus.     

Plasma levels of brain natriuretic peptide in various forms of obstruction to the left ventricular outflow tract

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship between plasma concentrations of brain natriuretic peptide (BNP) and the type or degree of stenosis in the left ventricular outflow tract (LVOT). METHODS: The relationship between BNP plasma level and pressure gradient (PG) in the LVOT and LV wall thickness (LVWth) was analyzed in 25 patients with a PG > or = 30 mmHg in the LVOT from the mid-left ventricle to the aortic valve. Among patients, 14 had aortic valve stenosis (AS), five had subaortic type hypertrophic obstructive cardiomyopathy (HOCM), three had mid-ventricular type HOCM, and three had angled ventricular septum. Three patients with AS showed LV systolic dysfunction (ejection fraction (EF) < 50%). All patients were in sinus rhythm. LV peak-systolic pressure (LVPSP) was derived by adding maximum PG to cuff systolic arterial pressure. RESULTS: In AS patients without LV systolic dysfunction and HOCM patients, there was a significant positive correlation between BNP and LVPSP (r = 0.78, p = 0.001; r = 0.76, p = 0.007, respectively). In AS patients without LV systolic dysfunction, BNP was positively correlated with LVWth (r = 0.79, p = 0.001), but no correlation was found between BNP and LVWth in patients with HOCM. In AS patients including systolic LV dysfunction, BNP was negatively correlated with LVEF (r = -0.87, p < 0.0001), but no correlation was found between BNP and LVEF in patients with HOCM. CONCLUSION: These results suggest that BNP level is closely associated with severity of stenosis in patients with HOCM, but mainly with severity of stenosis and also degree of LV systolic dysfunction in patients with AS. The BNP-LVWth relationship appeared to differ between AS (a fixed stenosis with uniform myocardial hypertrophy) and HOCM (a dynamic stenosis with uneven myocardial hypertrophy).     

Rituximab‐combination chemotherapy achieves a 10th cycle of remission for Burkitt's lymphoma

A 14‐year‐old girl with multiple intra‐abdominal tumors was diagnosed with stage III Burkitt's lymphoma. She achieved complete remission after multi‐drug chemotherapy, but she relapsed after six courses. Autologous peripheral blood stem cells (PBSC) or allogeneic PBSC harvested from an HLA‐identical sibling were insufficient, and her family did not agree to bone marrow collection from the sibling. Although the patient relapsed nine times (the relapses involved intra‐abdominal organs or bone) during the following 4 years 7 months, treatment with rituximab monotherapy or in combination with ifosphamide, carboplastin, and etoposide, or local irradiation (33.8–40.0 Gy) to treat the bone metastases, proved effective, resulting in complete or partial remission. At the time of writing, the patient was in a 10th cycle of remission lasting 1 year 6 months and had not required transplantation. Thus, a chemotherapy regimen including rituximab might be effective for Burkitt's lymphoma in patients experiencing multiple relapse.     

Neurodegenerative central nervous system disease as late sequelae of Langerhans cell histiocytosis. Report from the Japan LCH Study Group

Clinical features, brain magnetic resonance imaging findings and EDSS scores of 11 patients with neurodegenerative central nervous system Langerhans cell histiocytosis were analyzed in Japan. All patients initially had multi-system-type Langerhans cell histiocytosis; 8 at 1-2 years of age and 3 at a later age. Neurodegenerative central nervous system Langerhans cell histiocytosis disease developed after a median time interval of 3.9 years from initial diagnosis. With a median follow-up of 4.5 years, 6 patients showed progression of disease with an EDSS score >3. This study demonstrates the importance of early detection of neurodegenerative central nervous system Langerhans cell histiocytosis by brain magnetic resonance imaging, particularly in the follow-up of patients who developed multi-system-type Langerhans cell histiocytosis in early infancy.     

Asymmetrical Interstitial Lung Disease Suggested to Be Due to Hypoplasia of the Unilateral Pulmonary Artery: A Case Report with a 20-year Follow-up

We herein report a case of asymmetrical interstitial lung disease (ILD) that remained almost completely asymmetrical over time on chest computed tomography (CT). An open lung biopsy from the right lung showed severe pleural adhesion, obstruction of the pulmonary artery, and dilated systemic arteries in addition to the usual interstitial pneumonia pattern. Three-dimensional CT angiography showed partial defects of pulmonary arteries on the affected side. After excluding other known causes of ILD and gastroesophageal reflux, we suspected that decreased pulmonary artery perfusion in the present case may have been responsible for the observed asymmetrical unilateral fibrosis.